Involvement of brain glutamate release in pyrogenic fever

Whether the glutamate release in the organum vasculosum laminae terminalis (OVLT) is attributable to genesis of a pyrogenic fever is unclear. The lack of information led us to evaluate the changes in glutamate concentrations of OVLT during the fever induced by staphylococcal enterotoxin A (SEA) in u nanesthetized rabbits. Both the OVLT concentrations of glutamate and the co lonic temperatures were simultaneously monitored during systemic injection of SEA, MK801 (an N-methyl-D-aspartate (NIVIDA) receptor channel blocker), ketamine (an NMDA receptor channel blocker), or normal saline. The extracel lular dialysates in the brain were collected using a microdialysis probe pr eviously placed in the OVLT region. The concentrations of glutamate in the microdialysates were measured by a high-pressure liquid chromatography in c ombination with a fluorescence detector. Systemic administration of SEA (30 ng kg(-1) I.V.) increased both the concentrations of glutamate in the OVLT and the colonic temperatures. Glutamate appeared to rise slightly earlier than body temperature. Pretreatment or posttreatment with MK801 or ketamine significantly attenuated the SEA-induced augmenting glutamate release in t he OVLT and fever in rabbits. The suppression of glutamate release appeared to start slightly earlier than temperature decline. In addition, the SEA-i nduced fever could be mimicked by direct injection of glutamate or SEA into the OVLT area. The fever induced by intra-OVLT injection of SEA or glutama te was significantly attenuated by pretreatment with an intra-OVLT dose of MK801 (5 mug) or ketamine (10 mug). The results suggest that glutamatergic pathways in the OVLT region are in pyrogenic fever genesis. (C) 2001 Elsevi er Science Ltd. All rights reserved.